Approach

Hematopoietic stem cell transplantation (HSCT) or gene therapy are the only definitive treatments for patients with SCID.[8][47][48] HSCT is the principal therapy; gene therapy is an emerging technology.

Enzyme replacement therapy is available for patients with adenosine deaminase deficiency SCID.

Early diagnosis is critical, as infants who receive definitive treatment before the onset of infections have markedly improved long-term survival outcomes.[8][23][24]

Supportive measures before curative treatment

The management of patients diagnosed with SCID before successful curative treatment (HSCT or gene therapy) includes the following measures to help reduce the risk of infections until there is evidence of immunocompetence:[4][21][49]

  • Isolation from sick children and adults (hospitalization is not required)

  • Use of boiled, filtered water to prepare formula feeds

  • Immunoglobulin supplementation (may also be required after HSCT for persistent humoral immune deficiency)

  • Antibacterial prophylaxis

  • Antifungal prophylaxis

  • Antiviral prophylaxis

  • Avoiding live attenuated viral vaccines

  • If blood products are indicated, using irradiated blood products, leukocyte depleted, cytomegalovirus (CMV)-negative

  • Stopping breast-feeding, unless there is evidence that the mother is CMV negative.

HSCT

Overall survival rates of approximately 95% have been reported in patients who undergo HSCT for SCID within the first 3.5 months of life.[8][10]

Stem cell transplantation with a human leukocyte antigen (HLA)-matched sibling donor is preferred and has been shown in multiple studies to provide better engraftment, immune reconstitution, and overall survival than unrelated HLA-matched or related HLA-mismatched donors.[10][24][50][51] Five-year survival is greatest among those patients who received transplants from matched sibling donors (97%); the comparable figure for patients receiving grafts from unrelated donors is 58% to 79% (depending on graft source and T-cell depletion).[10]

Unfortunately, protocols for HSCT in patients with SCID are not uniform, and multicenter collaborative studies are needed to formalize treatment and obtain standard optimal approaches.[50][52]

Enzyme replacement therapy

Patients with adenosine deaminase deficiency SCID can undergo enzyme replacement therapy with pegylated adenosine deaminase (PEG-ADA).[53] However, it is not a definitive treatment, and serves as a temporary measure until definitive treatment (e.g., HSCT) can be performed.[12][53]

Treatment with PEG-ADA has been shown to decrease lymphotoxic metabolites (adenosine and deoxyadenosine), and restore enzyme activity.[54] PEG-ADA is available as elapegademase, a recombinant adenosine deaminase based on bovine amino acid sequence and conjugated to monomethoxypolyethylene glycol. It is approved for the treatment of adenosine deaminase deficiency SCID.

Long-term outcomes in patients treated with PEG-ADA have not been prospectively studied, but immune reconstitution appears to be variable.[55] In a European cohort, continued immune globulin replacement was required in 40% of patients treated with PEG-ADA for one year, and overall survival among those who received PEG-ADA alone (i.e., no HSCT) was 85%.[56] Patients receiving enzyme replacement therapy for ADA-deficient SCID gradually develop decreased levels of T cells, B cells, and natural killer cells with suboptimal proliferative responses.[54]

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